Evaluation of a standardized protocol for thrombin generation measurement using the calibrated automated thrombogram: An international multicentre study

Dargaud, Yesim; Wolberg, Alisa S.; Luddington, Roger; Régnault, V.; Spronk, Henri M. H.; Baglin, Trevor; Lecompte, T.; Cate, Hugo Ten; Négrier, Claude

doi:10.1016/j.thromres.2012.07.017

Cited by 113 publications

(141 citation statements)

References 34 publications

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“…Plasma artificially depleted in protein S was found to be hypercogulable due at least in part to the expected loss of APCindependent anticoagulant effect [21,22]. In agreement with previously published data [19] and ECAT TGT surveys, the lab-to-lab variability of raw results was important whatever the initiating conditions or types of plasma. Indeed, only few CVs were inferior to 10%, a maximal accepted target-value to allow multicentre studies.…”

Section: Discussionsupporting

confidence: 86%

“…To reduce lab-to-lab variability, normalisation of raw data with an appropriate plasma has been proposed [14,15,19]. In the herein reported study, participants had to normalise their data with external RP prepared by Diagnostica Stago and, if applicable, the locally prepared pool of normal plasma.…”

Section: Discussionmentioning

confidence: 99%

“…This external reference plasma is a lyophilised plasma selected to have a thrombin generation profile as close as possible to a fresh frozen normal donor plasma pool. It has been demonstrated to be suitable for such use by Dargaud et al [19].…”

Section: Reagentsmentioning

confidence: 99%

“…Normalisation of raw results using a normal plasma (pooled or lyophilised) has been proposed for that purpose [14][15][16][17][18]. Recently, a standardized protocol with normalisation of results using a reference plasma (RP) has been shown to reduce lab-to-lab variability [19]. Though promising, such data, obtained in a relatively small number of reference laboratories and using a single batch of reagents, remain distant from real life practice.…”

Section: Introductionmentioning

confidence: 99%

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Large external quality assessment survey on thrombin generation with CAT: further evidence for the usefulness of normalisation with an external reference plasma

Perrin

Depasse

Lecompte

et al. 2015

Thrombosis Research

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Calibrated Automated Thrombography (CAT) has been widely used to assess in vitro thrombin generation as an informative intermediary phenotype of coagulation. Interlaboratory exercises have documented a worrisome poor reproducibility. There are some data on the normalisation with an appropriate external reference plasma (RP). This multicentre study of the French-speaking CAT Club aimed at providing further evidence for the usefulness of such a normalisation

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Reagentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Large external quality assessment survey on thrombin generation with CAT: further evidence for the usefulness of normalisation with an external reference plasma

Perrin

Depasse

Lecompte

et al. 2015

Thrombosis Research

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“…Despite the fact that TGA is a known marker for thrombotic risk, clinical application has been limited because of poor interlaboratory standardization of assay techniques. [58][59][60] However, both serum albumin and proteinuria severity have been epidemiologically linked to thrombotic risk. [13][14][15][16][17][18] Thus, if confirmed, proteinuria and/or serum Figure 5.…”

Section: Discussionmentioning

confidence: 99%

Disease Severity Correlates with Thrombotic Capacity in Experimental Nephrotic Syndrome

Kerlin

Waller

Sharma

et al. 2015

Journal of the American Society of Nephrology

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Thrombotic disease, a major life-threatening complication of nephrotic syndrome, has been associated with proteinuria and hypoalbuminemia severity. However, it is not fully understood how disease severity correlates with severity of the acquired hypercoagulopathy of nephrotic syndrome. Without this knowledge, the utility of proteinuria and/or hypoalbuminemia as biomarkers of thrombotic risk remains limited. Here, we show that two well established ex vivo hypercoagulopathy assays, thrombin generation and rotational thromboelastometry, are highly correlated with proteinuria and hypoalbuminemia in the puromycin aminonucleoside and adriamycin rat models of nephrotic syndrome. Notably, in the puromycin aminonucleoside model, hyperfibrinogenemia and antithrombin deficiency were also correlated with proteinuria severity, consistent with reports in human nephrotic syndrome. Importantly, although coagulation was not spontaneously activated in vivo with increasing proteinuria, vascular injury induced a more robust thrombotic response in nephrotic animals. In conclusion, hypercoagulopathy is highly correlated with nephrotic disease severity, but overt thrombosis may require an initiating insult, such as vascular injury. Our results suggest that proteinuria and/or hypoalbuminemia could be developed as clinically meaningful surrogate biomarkers of hypercoagulopathy to identify patients with nephrotic syndrome at highest risk for thrombotic disease and potentially target them for anticoagulant pharmacoprophylaxis.

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Promising biomarkers for the prediction of catheter‐related venous thromboembolism in hospitalized children: An exploratory study

Nossair

Mahajerin

Hoang

et al. 2019

Pediatric Blood & Cancer

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Background: Pediatric venous thromboembolism (VTE) has increased over the past 10 years, with central venous catheters (CVC) being the strongest risk factor. Current tools are not sufficient to predict VTE risk. The utility of biomarkers in predicting CVC-related VTE has been minimally explored. Our objective is to determine the utility of microparticles (MPs), factor VIII (FVIII) activity, and thrombin generation (TG) in prospectively predicting VTE occurrence in hospitalized children with CVCs. Procedure:In this nested case-control pilot study, consecutive hospitalized children needing CVC placement (1 month to 21 years) were enrolled. Venous samples were collected prior to or within 24 h of CVC placement. MPs were measured using factor Xa initiated clot-based assay. FVIII was measured using a one-stage clot-based assay. TG was measured using calibrated automated thrombogram.Results: There were three CVC-related VTE events (7%) in our cohort of 42 subjects. Xa clotting time (XaCT) ratio was lower (0.68 ± 0.07 vs 0.95 ± 0.21, P = .4), while FVIII (461 ± 120 vs 267 ± 130, P = .02), peak thrombin (418 ± 89 vs 211 ± 101, P = .001), endogenous thrombin potential (ETP) (1828 ± 485 vs 1282 ± 394, P = .03), and velocity index (VI) (182 ± 28 vs 75 ± 53, P = .001) were higher in subjects with CVC-related VTE compared to those without CVC-related VTE. Sensitivity/specificity analysis revealed optimal cutoff values for XaCT ratio (0.75), FVIII (370), ETP (1680), peak (315), and VI (130), with receiver operating characteristic area under the curve values >0.9.Conclusion: MPs, FVIII, and TG can potentially predict pediatric CVC-related VTE in a prospective fashion. Stratification according to VTE risk may aid in guiding preventative efforts in future studies.

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Evaluation of a standardized protocol for thrombin generation measurement using the calibrated automated thrombogram: An international multicentre study

Cited by 113 publications

References 34 publications

Large external quality assessment survey on thrombin generation with CAT: further evidence for the usefulness of normalisation with an external reference plasma

Large external quality assessment survey on thrombin generation with CAT: further evidence for the usefulness of normalisation with an external reference plasma

Disease Severity Correlates with Thrombotic Capacity in Experimental Nephrotic Syndrome

Promising biomarkers for the prediction of catheter‐related venous thromboembolism in hospitalized children: An exploratory study

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